RNA on the move: the mRNA localization pathway [published erratum appears in J Cell Biol 1993 Dec;123(6 Pt 1):1625]
RNA on the move: the mRNA localization pathway [published erratum appears in J Cell Biol 1993 Dec;123(6 Pt 1):1625]
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发表时间：
1993-10
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通讯作者：
J. Wilhelm;R. Vale
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作者：
J. Wilhelm;R. Vale
长期以来，细胞学家一直对细胞如何将蛋白质靶向特定的细胞内区室并维持其局部分布着迷。蛋白质如何分类到特定的膜结合细胞器的问题一直是过去十年中大量努力的焦点。因此，人们对蛋白质分选信号 (48, 54)、分泌途径中囊泡出芽和对接所需的蛋白质机制 (48, 54) 以及沿着细胞质内的微管和肌动蛋白丝运输囊泡的机制 (55) 有了很多了解。与有关膜蛋白分类的相对丰富的信息相比，人们对胞浆蛋白如何在细胞质内分配知之甚少。然而，越来越清楚的是，mRNA 的运输，而不是翻译的蛋白质本身，构成了定位胞浆蛋白的重要手段（表 I）。细胞质 RNA 定位的第一个证据来自肌动蛋白转录物在海鞘胚胎中分布不均匀的发现 (29)。此后不久，在爪蟾 (53) 和果蝇 (17) 中鉴定出几种母体 mRNA，它们位于卵子发生过程中。最近，在体细胞中发现了定位的 mRNA（表 I），这清楚地表明 mRNA 定位是在细胞质中创建蛋白质不对称分布的一般机制（在最近的几篇评论中进行了讨论；42、58、62）。虽然 mRNA 定位已在许多系统中得到充分记录，但产生受限 RNA 分布的机制尚不清楚，mRNA 在随机扩散通过细胞质后可能会被局部捕获，或者它可能会沿着细胞骨架元件主动转运到其目标。通过直接观察细胞内 mRNA 的运动可以最好地区分这两种可能性。 Ainger 等人通过将编码髓磷脂碱性蛋白的荧光标记 mRNA 注射到少突胶质细胞中。 (1) 在本期《细胞生物学杂志》中报道，mRNA 形成进行单向运输的“颗粒”，类似于膜细胞器电机驱动运动的描述 (2, 69)。这些观察结果以及其他研究人员的相关工作表明，mRNA 定位存在一条有序的途径（见图 1），包括：（a）RNP 颗粒的形成； (b) 粒子移位至目的地； (c) 将颗粒锚定至细胞骨架； (d) 本地化的翻译
IOLOGISTS have long been fascinated by how cells target proteins to specific intraeellular compartments and maintain their localized distributions. The problem of how proteins are sorted to particular membranebound organelles has been the focus of considerable effort in the last decade. As a result, a good deal is known about protein sorting signals (48, 54), the protein machinery needed for budding and docking vesicles in the secretory pathway (48, 54), and the mechanisms for transporting vesicles along microtubules and actin filaments within the cytoplasm (55). In contrast to the relative wealth of information concerning the sorting of membrane proteins, very little is understood about how cytosolic proteins are partitioned within the cytoplasm. However, it has become increasingly clear that the transport of mRNAs, and not the translated proteins themselves, constitutes an important means of localizing cytosolic proteins (Table I). The first evidence for cytoplasmic RNA localization came from the finding that actin transcripts are unevenly distributed in the ascidian embryo (29). Shortly thereafter, several maternal mRNAs were identified in Xenopus (53) and Drosophila (17) that are localized during oogenesis. More recently, localized mRNAs have been discovered in somatic cells (Table I), making it clear that mRNA localization serves as a general mechanism for creating asymmetric distributions of proteins in the cytoplasm (discussed in several recent reviews; 42, 58, 62). While mRNA localization has been well documented in many systems, the mechanism that generates restricted RNA distributions is less well understood, mRNA could become locally trapped after diffusing randomly through the cytoplasm, or it could be actively transported along cytoskeletal elements to its target. These two possibilities can be best distinguished by directly visualizing the movements of mRNA within cells. By injecting fluorescenfly labeled mRNA encoding myelin basic protein into oligodendrocytes, Ainger et al. (1) report in this issue of the Journal of Cell Biology that mRNA forms "particles" that undergo unidirectional transport, similar to that described for motor-driven movements of membranous organelles (2, 69). These observations, as well as related work by other investigators, suggest that there is an ordered pathway (see Fig. 1) for mRNA localization consisting of: (a) formation of a RNP particle; (b) translocation of the particle to its destination; (c) anchoring of the particle to the cytoskeleton; and (d) translation of the localized